A primary goal in conditioned learning research is to understand the principles underlying how organisms acquire and express learned behaviors. Pavlovian fear conditioning, for instance, has served as a model system for the study of how humans learn to fear otherwise innocuous stimuli through the process of contingency learning between a neutral cue and a biologically aversive stimulus. Significant progress has been made in unraveling the neurobiological basis of fear learning, and recent advances in cognitive neuroscience have informed behavioral treatments for clinical anxiety disorders ranging from specific phobias to posttraumatic stress disorder. The Specific Aims within this proposal are designed to extend knowledge of the behavioral and brain mechanisms involved in human fear learning by directly investigating processes supporting the generalization of learned fears. These investigations will explore how humans generalize to neutral objects that approximate a feared stimulus using psychophysiology and functional magnetic resonance imaging (fMRI) methods. We will uncover the biobehavioral and brain mechanisms involved in generalizing fear in the attempt to better characterize clinical disorders marked by exaggerated fear responses to neutral cues. In these studies, participants will learn that a particular object is fear relevant using Pavlovian fear conditioning methods. Subsequently, participants will be exposed to a range of objects that deviate from the fear conditioned object along a dimension of perceptual similarity (Aim 1) or semantic relatedness (Aim 2 and Aim 3). Individual differences in fear generalization will be assessed by constraining our interpretations of brain activity with behavioral psychophysiology measures. Furthermore, a primary goal in all three Aims is to investigate not only how humans generalize fear, but also learn to control fear responses to objects that are perceptually or conceptually related to a feared stimulus. PUBLIC HEALTH RELEVANCE: The proposed research contributes to a greater understanding of mental health disorders marked by heightened expression of fear. These neuroimaging investigations attempt to uncover the brain mechanisms supporting the generalization of fear from a known fear-relevant stimulus to emotionally neutral stimuli that approximate the feared stimulus, either perceptually or semantically. A greater recognition of how generalization modulates the cognitive processes involved in fear expression will strengthen understanding of certain mental health disorders (e.g. specific phobias and posttraumatic stress disorder) and may lead to model systems important for the treatment and prevention of these disorders.